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Beta 2-adrenergic receptors on eosinophils. Binding and functional studies
1Department of Thoracic Medicine, National Heart and Lung Institute, Brompton Hospital, London, United Kingdom.
The American Review of Respiratory Disease
|June 1, 1990
Summary
Human and guinea pig eosinophils have beta-2 adrenoceptors linked to adenylate cyclase, but these receptors do not affect oxidative metabolism or degranulation, suggesting limited therapeutic potential for asthma treatments targeting these pathways.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Eosinophils play a role in inflammatory diseases like asthma.
- Beta-adrenoceptors are targets for asthma medications.
- The function of beta-adrenoceptors on eosinophils is not fully understood.
Purpose of the Study:
- To investigate the presence and function of beta-adrenoceptors on human and guinea pig eosinophils.
- To determine if beta-adrenoceptor activation influences eosinophil oxidative metabolism and degranulation.
Main Methods:
- Radioligand binding assays using [125I]pindolol (IPIN) to quantify beta-adrenoceptors.
- Scatchard analysis to determine receptor binding kinetics (Kd, Bmax).
- Measurement of cyclic AMP (cAMP) levels following beta-agonist stimulation.
- Assessment of superoxide anion generation and eosinophil peroxidase release after stimulation with zymosan or PMA, with or without albuterol.
Main Results:
- Eosinophils from humans and guinea pigs possess a single class of beta-adrenoceptors with high affinity for IPIN.
- Binding studies and antagonist selectivity (ICI 118,551 vs. atenolol) indicate these are predominantly beta-2 adrenoceptors.
- Beta-2 agonists (isoproterenol, albuterol) increased cAMP levels, confirming coupling to adenylate cyclase.
- Albuterol did not inhibit superoxide anion generation or eosinophil peroxidase release induced by zymosan or PMA.
Conclusions:
- Human and guinea pig eosinophils express functional beta-2 adrenoceptors coupled to adenylate cyclase.
- These beta-2 adrenoceptors do not modulate eosinophil oxidative burst or degranulation.
- The findings suggest that targeting eosinophil beta-2 adrenoceptors may have limited therapeutic benefit in asthma by modulating these specific functions.